Drug distribution, changing methods

Controlled-release polymer implants are useful for delivering drugs directly to the brain interstitium. This approach may improve the therapy of brain tumors or other neurologieal disorders. The mathematical models described in this section—which are based on methods of analysis developed in earlier chapters—provide a useful framework for analyzing mechanisms of drug distribution after delivery. These models describe the behavior of chemotherapy compounds very well and allow prediction of the effect of changing properties of the implant or the drug. More complex models are needed to describe the behavior of macromolecules, which encounter multiple modes of elimination and metabolism and are subject to the effects of fluid flow. 

A drug-induced change in the distribution and renal excretion of sulfonamides, JPET, 134, 291-303 (1961). Mayer et al. also reported values for thiopental (7.6), aniline (4.6), aminopyrine (5.1), 4-aminoantipyrine (4.1), acetanilide (1.0), barbital (7.8), N-acetyl-4-aminoantipyrine (NAAP 0.5), salicylic acid (3.0). With the exceptions of acetanilide and NAAP, all additional pKa values were obtained by the potentiometric method. The barbital value is lower than the best value and suggests that carbon dioxide absorption interfered, however, the remaining values should not be affected by this factor. 

These variables can be minimized by design changes to the standard experimental protocol. It has been shown that utilization of smaller volumes, collected at least 4 mm from the round window, produces negligible CSF contamination. These small sample aliquots will yield more consistent drug concentrations regardless of differences in drug distribution (Salt et al. 2003). Additionally, although methods... 

The first attempt to radiolabel drug particles (instead of polymers like polystyrene or Teflon particles) for pharmaceutical aerosols was carried out on fenoterol and salbutamol by Kohler et al. [12] Scheme 3). However, it was later found that their method would change the particle size distribution of the labelled aerosol, resulting in a coarser aerosol than the imlabelled product. After subsequent improvement by Summers et al. [18] Scheme 4), this method has become widely used for radiolabelling MDIs. It is preferred over other methods as it does not involve extraction with tetraphenylarsonium chloride and chloroform. 

An interesting application of speciation is in the study of changes in the distribution of certain metals after administration of drugs. Falchuk used gel filtration combined with flame atomic absorption spectrometry to study effects of the administration of ACTH on the zinc distribution in serum. Kamel et ai. developed methods to follow the distribution of gold. 

In the field of site-specific drug delivery there is considerable research effort invested in the development of methods of changing microparticle surface chemistry with the aim of altering the distribution of the particles within the body... 

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